Approximately 15 percent of patients recover from hepatitis C virus (HCV) infection while 85 percent become persistently infected with various degrees of associated chronic liver disease. In this study, comparisons will be made between patients who rapidly recover, those who have delayed recovery, those with persistent infection and stable chronic disease, and those with rapidly progressive, fatal infection. The parameters measured will be viral burden (initially and over time), HCV genotype, the number of viral quasispecies (extent of viral heterogeneity) at the time of infection and subsequently, neu-tralizing antibody responses, and, if appropriate technology is available, cytotoxic T cell responses. The goal is to determine if any of these parameters can predict outcome. Studies to date have shown no correlation with genotype because the population is fairly homogeneous for HCV genotype 1. However, there does appear to be a correlation between viral quasispecies and disease outcome. Using rare specimens obtained during the first 16 weeks of HCV infection, it has been shown that the greater the number of viral variants (quasispecies) and the greater the complexity of the sequence divergence, the more severe the clinical out-come. It is believed that the quasispecies is driven by immune pressure and it may be that immune pressure that is intense, and yet insufficient to clear the virus, leads to more severe liver disease either as the result of cell-mediated cytotoxicity or the selection of more pathogenic viral variants.